10-68911239-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_024045.2(DDX50):c.632C>T(p.Ser211Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00029 in 1,595,568 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00030 ( 2 hom. )
Consequence
DDX50
NM_024045.2 missense
NM_024045.2 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: 4.94
Genes affected
DDX50 (HGNC:17906): (DExD-box helicase 50) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box enzyme that may be involved in ribosomal RNA synthesis or processing. This gene and DDX21, also called RH-II/GuA, have similar genomic structures and are in tandem orientation on chromosome 10, suggesting that the two genes arose by gene duplication in evolution. This gene has pseudogenes on chromosomes 2, 3 and 4. Alternative splicing of this gene generates multiple transcript variants, but the full length nature of all the other variants but one has not been defined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.16246074).
BS2
High Homozygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DDX50 | NM_024045.2 | c.632C>T | p.Ser211Leu | missense_variant | 4/15 | ENST00000373585.8 | NP_076950.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DDX50 | ENST00000373585.8 | c.632C>T | p.Ser211Leu | missense_variant | 4/15 | 1 | NM_024045.2 | ENSP00000362687.3 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152084Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000855 AC: 20AN: 233950Hom.: 0 AF XY: 0.0000866 AC XY: 11AN XY: 126950
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GnomAD4 exome AF: 0.000304 AC: 439AN: 1443366Hom.: 2 Cov.: 31 AF XY: 0.000300 AC XY: 215AN XY: 717768
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74398
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 28, 2024 | The c.632C>T (p.S211L) alteration is located in exon 4 (coding exon 4) of the DDX50 gene. This alteration results from a C to T substitution at nucleotide position 632, causing the serine (S) at amino acid position 211 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at